The supplement will provide the resources necessary to take advantage of the unique opportunities afforded by this consortium to evaluate the genetic factors that contribute to the development and progression of B cell chronic lymphocytic leukemia (CLL). There are two major objectives for this supplement. First, we propose to collect all suitable clinical data and clinical specimens from patients with familial CLL for targeted studies performed by Dr. Carlo Croce and associates (Project l) and by Dr. Neil Caporaso and associates of the NCI Genetic Epidemiology Branch. Second, we will evaluate for the genetic changes that are responsible for the pathogenesis and progression of B cell CLL. This will involve analyses of familial CLL genomic samples for mutations/polymorphism in genes that have been identified as potentially involved in sporadic CLL and for genetic polymorphism identified via high-throughput genomic screening and linkage analyses performed by intramural investigators at the NCI. Finally, this objective also will require analyses of gene expression profiles in leukemia cells from selected paired sibships of familial CLL and targeted cases of sporadic CLL that demonstrate different kinetics of diseases progression. Through these studies we should identify genetic factors that contribute to the development and progression of B cell CLL.